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Volume 1, Issue 15

 

Cover Image

Cover Figure: Model of evolution from clonal hematopoiesis of indeterminate potential (CHIP) to therapy-related myeloid neoplasms. See the article by Takahashi et al.

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WASHINGTON, June 27,  2017 – Welcome to the “Advance Notice,”  newsletter which provides highlights from issues of Blood Advances, the open-access journal of the American Society of Hematology (ASH), that  are hand-picked by Blood Advances Editor-in-Chief Robert Negrin, MD.

Inotuzumab ozogamicin (InO) is directed against CD22-expressing malignancies. In the study by DeAngelo and colleagues, InO was evaluated in adults with relapsed refractory CD22–positive acute lymphoblastic leukemia, demonstrating that this agent is well tolerated and has single-agent activity resulting in minimal residual disease–negative remissions in some patients. Further studies will be needed to define the role of this agent in the arsenal of active agents to treat this challenging disease.

Thrombotic thrombocytopenic purpura is a life-threatening disease with a significant risk of relapse after initial treatment. Rituximab has been shown to be an effective approach to prevent relapse in high-risk patients. Westwood et al explore the dosing regimen of rituximab to prevent disease recurrence.

Acute myelogenous leukemia (AML) is associated with high levels of CD123 (interleukin-3 [IL-3] receptor α) expression, which is being explored as a therapeutic target. Wittwer et al investigated the biological basis for poorer prognosis in patients with high CD123 expression. They found that AML cells are more proliferative and have increased survival at low IL-3 concentrations, along with altered migratory properties.

Immune cells function within specific immunological niches, resulting in important interactions and growth signals. This paper by Adutler-Lieber et al explores the role of different cytokines and intracellular signaling within the immune niche, highlighting critical roles for CCL21, ICAM-1, and interleukin-6 in T-cell expansion. These results have important biological relevance and could lead to better expansion and function of therapeutic T cells.

Adult T-cell leukemia is a T-cell malignancy caused by infection by human T-lymphotropic virus 1 (HTLV-1). However, only about 5% of infected patients develop leukemia. Firouzi and colleagues  studied a series of patient samples. They found that individuals with clonal infection are much more likely to develop leukemia and thus that clonal infection serves as a useful indicator of eventual disease progression.

Clonal hematopoiesis of indeterminate potential has emerged as an important risk factor for the development of subsequent myeloid malignancies. In this study by Takahashi et al, other genetic markers were also observed in some patient samples, further defining risk determinants of disease progression.

Erythroid progenitors are a major consumer of iron in the body. Recent studies have demonstrated a role for both transferrin receptors 1 and 2. In this study by Khalil et al, a detailed analysis of transferrin receptor 2–mediated lysosomal transferrin delivery yields important new findings.

 

Autologous hematopoietic cell transplantation is a well recognized therapy for patients with multiple myeloma that has been validated in a number of randomized clinical trials. However, what is less clear is why some patients enjoy very long term remission and others do not. The study by Ho et al argues that progression free and overall survival is largely influenced by immunological parameters that suggests many therapeutic possibilities.

Umbilical cord blood transplantation has been a successful alternative stem cell source. However, it has been associated with relatively slow hematopoietic engraftment. One approach has been to use CD34+ cells from a haploidentical family donor in addition to the umbilical cord blood unit (Haplo-Cord). Sanz et al present a retrospective analysis of outcomes of these different approaches, with interesting results.

 

Should ovarian vein thrombosis be treated? Check out the discussion by Plastini and colleagues.

 

In a Commentary, Sachais et al discuss the implications of the Food and Drug Administration’s guidance for mitigating septic shock after platelet transfusions. How will these guidelines impact the availability of this precious resource?

Featured Visual Abstract

Factor VIIa interaction with EPCR modulates the hemostatic effect of rFVIIa in hemophilia therapy: mode of its action

Shiva Keshava, Jagan Sundaram, Anuradha Rajulapati, Charles T. Esmon, Usha R. Pendurthi and L. Vijaya Mohan Rao

 

 

 

Blood Advances is the open-access journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.

ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.